Similar type compounds, particularly (3-amino-5-substituted-6-halopyrazinoyl)guanidines and (3-amino-5-substituted-6-halopyrazinamido)guanidines have been disclosed in U.S. Pat. Nos. 3,313,813 and 3,300,494, respectively. However, in neither patent is applicants' (3-amino-5-substituted-6-fluoropyrazinoyl)guanidine or pyrazinamido-guanidines disclosed.
In U.S. Pat. No. 3,313,813 the 6-fluoro derivative has not been claimed or disclosed because the 6-position was described in col. 1 lines 28-30 of said patent as halogen or halogen-like radicals, such as chloro, bromo, iodo or trifluoromethyl.....
Similarly in U.S. Pat. No. 3,300,494, although the 6-halo derivative was claimed in the specification in col. 1, lines 20-22, the 6-substituent is described as a halogen substituent such as chlorine, bromine, iodine, or a trihalomethyl radical.... Nowhere in these patents is a 6-fluoro derivative specifically disclosed or claimed. In fact, none could be specifically disclosed as at that time, the immediate precursor needed for preparing applicants' compounds, namely the lower alkyl-3-amino-5-substituted-6-fluoro pyrazinoates was unknown. At the time of filing the two U.S. patents mentioned above, a method for introduction of a 6-fluoro group onto the pyrazinoate was not known.
A unique and unexpected advantage of the (3-amino-5-substituted-6-fluoropyrazinoyl or pyrazinamido)guanidines of this invention in comparison to other 6-halo analogs is their markedly lower toxicities. For example, the acute oral toxicity of (3,5-diamino-6-chloropyrazinoyl)guanidine in mice is over ten times as toxic as the corresponding 6-fluoro analog.